This proposal addresses the thesis that chronic inflammatory processes - common in an aging population - accelerates the development of atherosclerosis. Inflammation can either be systemic such as that associated with chronic rheumatic diseases, or localized in the early atherosclerotic lesions. Here lipid peroxidation triggers the expression of inflammatory genes that are likely involved in atherogenesis. Inflammatory induces a wide variety of metabolic changes with two of these changes relating specifically to modulation of HDL metabolism. These are the concomitant induction of cytokines of secretory non-pancreatic phospholipase A2(sPLA2) and serum amyloid A protein (SAA). Both these proteins increase hundreds of fold- in inflammatory fluids and the circulation and markedly romodels the HDL particle. The metabolic implications of such remodeling is of obvious importance given that HDL is associated with protein against the development of atherosclerosis. Substantial evidence exists that phospholipaseA2 hydrolysis of HDL promotes lipid delivery by this particle to cells. The investigators propose that this modulation of HDL by sPLA2 and SAA is beneficial for the acute defense and repair process. However, when sPLA2 and SAA are aberrantly produced during chronic inflammatory diseases or in early atherosclerotic lesions, lipid delivery by these normally defensive molecules promotes atherogenesis. The investigators confirmed the relevance of this lipid delivery to atherogenesis in a human sPLA2 overexpressing transgenic mouse model of this disease. Vascular lipid deposition in this model was five times more in the sPLA2 overexpressing mice when compared to littermates in the response to a high fat diet. This proposal seeks to explore the importance of this finding in greater depth and to study two mechanisms that could explain this enhanced vascular lipid deposition.